P558: ABSOLUTE LYMPHOCYTE COUNT IS AN INDEPENDENT SURVIVAL PREDICTOR COMPARED TO MINIMAL RESIDUAL DISEASE IN PATIENTS WITH ACUTE MYELOID LEUKEMIA TREATED WITH INTENSIVE CHEMOTHERAPY
Authors: Gianluca Cristiano, Jacopo Nanni, Letizia Zannoni, Federico Zingarelli, Chiara Sartor, Parisi Sarah, Stefania Paolini, Cristina Papayannidis, Michele Cavo, Antonio Curti
Journal: HemaSphere (2023)

Background: Absolute lymphocyte count (ALC)is known to be an independent prognostic factor for overall survival (OS) in patients receiving autologous transplantation for lymphomas as for many solid cancers. In acute myeloid leukemia (AML) patients, enhanced ALC recovery after intensive chemotherapy (IC) has been associated with superior OS. However, few if any data correlated ALC recovery with updated prognostic factors, such as European Leukemia Net (ELN) risk-classification and minimal residual disease (MRD). Aims: Our study aims at evaluating ALC recovery in newly diagnosed AML patients who were responsive to IC by analysing its impact through different patient subgroups according to type of chemotherapy regimen, allogeneic stem cell transplantation (HSCT) and MRD. Methods: We evaluated 156 AML patients from Bologna Seràgnoli Hematology Institute since 2007. Our selection of patients who obtained complete remission (CR) was due to the poorly evaluable data in refractory ones and to the possibility of assessing the impact of ALC recovery on MRD achievement. MRD was evaluated by RT-PCR specific transcripts or WT1. We defined 4 ALC time-points (TPs): at 15, 21 and 28 days from IC start and before consolidation therapy (CC). ALC cut-off was 500/mm3. Patients were also grouped in those who obtained ≥500/mm3ALC in all 4 TPs and those who had<500/mm3ALC in at least one TP. Median follow-up was 65 months. Results: We subdivided patients according to IC regimen: “3 + 7-based” (52,6%) versus “fludarabine-based” (47,4%) therapy. Considering “3 + 7” subgroup, at ALC-15 a significant correlation with OS (p=0.047) of patients with ≥500/mm3ALC (34,6%) vs those under the cut-off (17,9%) was observed. A similar pattern was shown in patients with ALC≥500/mm3 in all 4 TPs (27,5%)compared to those who had <500/mm3ALC in at least one TP (25%)(p=0.021). Among patients treated with a “fludarabine-based” regimen, ALC recovery has rather shown a totally inverted correlation trend compared to “3 + 7”, with a significant better outcome of patients who had <500/mm3ALC. We also analysed the impact of ALC recovery in patients who received HSCT (63,5%) vs those who did not (36,5%) (Fig.1). In HSCT patients the impact of ALC recovery was minimal (blue and purple curve). In contrast, patients who had ALC <500/mm3 in at least one TP and did not undergo HSCT had the worst outcome (green curve), while, interestingly, those with ≥500/mm3ALC in all 4 TPs (red curve) had a better OS, which is comparable to transplanted ones. Lastly, we correlated ALC recovery with MRD value after two therapy courses. Notably, considering patients who obtained MRD negativity among “3 + 7” subgroup (n = 45), those who had ≥500/mm3ALC in all ALC TPs (n=27) and in ALC-15 (n=32) resulted in better OS if compared to the corresponding patients with <500/mm3 ALC at the two different time-points (n=18 and n=13, respectively)(p=0.04 and p=0.06, respectively; Fig.2). Among the different groups, no significant differences regarding age, ELN risk, cytogenetics, HSCT consolidation rate were identified. Summary/Conclusion: Our study indicates ALC recovery during and after IC as a promising survival predictor in AML patients, who achieve CR and do not undergo HSCT. In particular, ALC is an independent OS predictor in patients who obtain MRD negativity. The type of IC regimen (3 + 7 versus fludarabine-based) impacts the clinical relevance of ALC recovery, which may be explained by the well-known lymphocytolytic effect of fludarabine. To confirm ALC predictive value according to ELN 2022 risk-stratification, the use of novel drugs (such as FLT3 inhibitors), MRD status and HSCT, a study on a larger cohort of patients is on-going.Keywords: Minimal residual disease (MRD), Absolute lymphocyte count, Acute myeloid leukemia, Allogeneic hematopoietic stem cell transplant